The objective of this program is to develop an antibacterial drug suitable for the treatment of antibiotic-resistant staphylococcal and enterococcal infections in hospitalized patients. At present there is a growing threat from these multiple antibiotic-resistant infections, and the 6-anilinouracil drugs being developed through Microbiotix research are bactericidal and equally effective against antibiotic-resistant and sensitive clinical isolates of the relevant organisms. The 6-anilinouracils selectively inhibit a novel and essential Gram-positive bacterial target, DNA polymerase III, and thus, represent an entirely new class of Gram-positive-selective antimicrobials. The immediate goal of the current program is to establish that two promising 6-anilinouracils have an in vivo efficacy and therapeutic index to qualify for further preclinical drug development. The specific aims of the current program are: (1) to formulate two drug candidates to enhance their in vivo bioavailability, and (2) to use these formulated preparations to: (a) establish the drugs' pharmacokinetic profiles, (b) evaluate their in vivo antibacterial efficacy for the treatment of staphylococcal and enterococcal infections with clinically relevant multiple antibiotic-resistant strains, and (c) to profile their acute and chronic toxicity in mice.